On December 10, 2019 Ascentage Pharma (6855.HK), a globally-focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that the updated results from the Phase I study of the company’s novel investigational drug HQP1351 were reported in an oral presentation at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (Press release, Ascentage Pharma, DEC 10, 2019, View Source [SID1234552212]). The presentation titled "Updated Safety and Efficacy Results of Phase I Study of HQP1351, a Novel 3rd Generation BCR-ABL Inhibitor in Patients with Tyrosine Kinase Inhibitor-Resistant Chronic Myeloid Leukemia" was delivered by the principal investigator of the study, Qian Jiang, M.D., from Peking University People’s Hospital. In addition, the presentation data was nominated for the "Best of ASH (Free ASH Whitepaper)", a recognition that only a handful of innovative clinical programs from China have achieved.

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HQP1351 is a novel, orally active potent 3rd generation BCR-ABL Tyrosine Kinase Inhibitor (TKI) under development for the treatment of patients with chronic myeloid leukemia (CML) resistant to current TKI-therapies including those with T315I mutation.

Key results from the trial:

The study is a Phase 1 trial of HQP1351 in Chinese patients with TKI-resistant CML in the chronic phase (CP) or accelerated phase (AP). Patients received treatment in one of the eleven dose cohorts ranging from 1mg to 60mg. 60mg QOD was identified as the dose-limiting toxicity (DLT) dose, 50mg QOD was considered as the maximum-tolerated dose (MTD), and 40mg was identified as RP2D;
As of May 27, 2019, 101 CML patients including 87 CP patients and 14 AP patients were enrolled in the study. The median duration of follow-up was 12.8 months (range, 1.2-31.5). The 18-month progression free survival (PFS) rate was 94% in CP and 61% in AP;
HQP1351 was well-tolerated in all dose cohorts with the exception of the 60mg cohort. Of all the treatment-related adverse events (TRAEs), most of the non-hematologic TRAEs were reported as Grade 1 or Grade 2; the most common hematologic TRAE of Grade 3/4 was thrombocytopenia (50%). The incidence of TRAEs declined with longer duration of treatment. No treatment-related deaths or Grade 5 AEs occurred;
HQP1351 showed potent anti-leukemic activities and a high response rate in TKI-resistant CML patients. The response rate and the depth of responses were further improved with longer duration of treatment. In the evaluable patients, the complete hematologic response (CHR) rate was 95% in CP and 85% in AP;
In the 95 evaluable patients with non-complete cytogenetic response (non-CCyR) at baseline, 69% of the CP patients achieved a major cytogenetic response (MCyR), of which 61% achieved a complete cytogenetic response (CCyR); 43% of the AP patients achieved MCyR, of which 36% achieved CCyR;
In the evaluable patients, the major molecular response (MMR) rate was 37% in CP and 36% in AP;
HQP1351 showed strong response in TKI-resistant CML patients with the T315I mutation. Among the T315I-mutant CP patients, the MCyR rate was 82%, and the CCyR rate was 78%.
"Drug-resistance to TKIs is an urgent unmet need and a major challenge in the treatment of CML. No third-generation TKI is currently approved in China, and no imported third-generation TKIs are expected to enter China in the foreseeable future," said presenting author Dr. Qian Jiang. "The updated results from this Phase I trial of HQP1351 have further validated its tolerability and anti-leukemic potential in refractory chronic myeloid leukemia. We look forward to collecting additional data from the pivotal Phase II trials and hope our work will soon benefit drug-resistant CML patients."

"The Phase I results on this third-generation BCR-ABL inhibitor have further demonstrated its clinical promise. HQP1351 returned to ASH (Free ASH Whitepaper) this year with an oral presentation and a nomination for ‘Best of ASH (Free ASH Whitepaper)’, all of which reaffirms the recognition of HQP1351’s potential clinical efficacy and safety by the international hematology community," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "There are three ongoing pivotal Phase II trials of HQP1351 in China, two of them have reached planned enrollment targets. The data readouts as well as an NDA submission in China are expected in 2020. In addition, the clinical development program of HQP1351 in the U.S. is ready to begin its patient enrollment. We hope HQP1351 will soon get the regulatory approval and reach the market to benefit drug-resistant CML patients in China and around the world."

About HQP1351

HQP1351 is a novel kinase inhibitor developed by Ascentage Pharma. It is an oral third-generation BCR-ABL inhibitor targeting a broad spectrum of BCR-ABL mutants, including those with the T315I mutation, to treat drug-resistant CML patients. A Phase I clinical trial for patients with TKI-resistant CML has been completed and the pivotal Phase II clinical trials are ongoing in China. In addition, a Phase Ib trial in patients with GIST and a Phase Ib trial are also ongoing in China and in the U.S., respectively.